A Gene to Explain Depression

As powerful as genes are in exposing clues to diseases, not even the most passionate geneticist believes that complex conditions such as depression can be reduced to a tell-tale string of DNA.

But a new study confirms earlier evidence that a particular gene, involved in ferrying a brain chemical critical to mood known as serotonin, may play a role in triggering the mental disorder in some people.

Researchers led by Dr. Srijan Sen, a professor of psychiatry at University of Michigan, report in the Archives of General Psychiatry that individuals with a particular form of the serotonin transporter gene were more vulnerable to developing depression when faced with stressful life events such as having a serious medical illness or being a victim of childhood abuse. The form of the gene that these individuals inherit prevents the mood-regulating serotonin from being re-absorbed by nerve cells in the brain. Having such a low-functioning version of the transporter starting early in life appears to set these individuals up for developing depression later on, although the exact relationship between this gene, stress, and depression isn’t clear yet. (More on Time.com: How to Win Friends: Have a Big Amygdala?)

Sen’s results confirm those of a ground-breaking study in 2003, in which scientists for the first time confirmed the link between genes and environment in depression. In that study, which involved more than 800 subjects, individuals with the gene coding for the less functional serotonin transporter were more likely to develop depression following a stressful life event than those with the more functional form of the gene. But these findings were questioned by a 2009 analysis in which scientists pooled 14 studies investigating the relationship between the serotonin transporter gene, depression and stress, and found no heightened risk of depression among those with different versions of the gene.

Sen’s group decided to put the continued controversy to rest by culling all of the available studies on the subject, 54 total, which included data from nearly 41,000 volunteers. Based on this broader analysis, the team concluded that the less functional form of the transporter gene does indeed confer a greater risk of depression when combined with stress. And to determine why the 2009 team found contradictory results, Sen also re-evaluated their data using his analytical model and found that when he limited his investigation to their 14 studies, he also found no relationship between the gene and depression. (More on Time.com: Placebos Work Even if You Know They’re Fake: But How?)

“One of the hopes I have is that we can settle this story, and move on to looking more broadly across the genome for more factors related to depression,” he says. “Ideally we would like to find a panel of different genetic variations that go together to help us predict who is going to respond poorly to stress, and who might respond well to specific types of treatment as opposed to others.”

He believes that the 2009 findings do not contradict those from 2003, or the latest results, but rather reflect a difference in the way the study was conducted. In order to conduct a consistent analysis with similarly collected data, the 2009 analysis focused only on the 14 studies that included stressful life events, and did not incorporate other stressors, such as childhood abuse or medical illness. The more complete set of 54 studies, which folded in these stressors as well, showed a robust interaction between the serotonin gene, stress and depression.

Sen stresses, however, that this gene is only one player in the cast of genetic and environmental factors that contribute to depression. “All things considered, this [gene] is a relatively small factor, and for this finding to be clinically useful, we really need to find many, many more factors. Ultimately we may identify new pathways that are involved in depression to come up with new and better treatments.”